The proposed research consists of two groups of studies that deal with Control of Breathing. The first group of studies explores the response of the human respiratory system to changes in its mechanical properties in the conscious state. Specifically, we shall address the following questions: 1) Do normal subjects alter their "inspiratory output" in the course of progressively increasing resistive and elastic loads, prior to perception of the load? 2) If so, is the response altered in patients with spinal injury? 3) What are the qualitative and quantitative differences in "inspiratory output" between normal subjects and patients with stable obstructive and restrictive disease? Our investigation of these problems will be greatly facilitated by use of a method, we recently developed, for quantitating "inspiratory output." The method permits the evaluation of qualitative and quantitative changes in inspiratory activity, throughout the breathing cycle, without being invasive. Our objective is to clarify the mechanisms by which the respiratory system copes with changes in its mechanical properties, and, by extension, the mechanisms of respiratory failure. The second group deals with the basic processes responsible for the sequential alternation between inspiration and expiration and involves detailed examination of the manner with which several inputs are handled by the respiratory oscillator. Special attention will be given to the threshold and integrative properties of the oscillator and to the reversibility of the observed effects. Specifically, we shall test the response to stimulating 3 inspiratory terminating systems namely, sympathetic, intercostal, and laryngeal afferents. In each case inspiratory activity, and the threshold for terminating this activity, will be measured at frequent intervals during and following application of the stimulus. The results should help narrow the possible mechanisms by which respiratory rhythm may originate and clarify the mode of action of different respiratory modulating inputs.